Molecular Epidemiology of Hypervirulent Carbapenemase-Producing Klebsiella pneumoniae

Abstract

ObjectiveTo investigate the overall distributions of key virulence genes in Klebsiella pneumoniae, especially the hypervirulent blaKPC-positive K. pneumoniae (Hv-blaKPC(+)-KP).MethodsA total of 521 complete genomes of K. pneumoniae from GenBank were collected and analyzed. Multilocus sequence typing, molecular serotyping, antibiotic-resistance, virulence genes and plasmid replicon typing were investigated.ResultsPositive rates of virulence genes highly varied, ranging from 2.9 (c-rmpA/A2) to 99.6% (entB). Totally 207 strains presented positive fimH, mrkD, entB and wzi and 190 showed positive fimH, mrkD, entB, irp2 and wzi, which were the two primary modes. A total of 94, 165 and 29 strains were denoted as hypervirulent K. pneumoniae (HvKP), blaKPC(+)-KP and Hv-blaKPC(+)-KP. ST11 accounted for 17 among the 29 Hv-blaKPC(+)-KP strains; Genes iucA, p-rmpA2 and p-rmpA were positive in 28, 26 and 18 Hv-blaKPC(+)-KP strains respectively. Among the 29 Hv-blaKPC(+)-KP strains exhibiting four super clusters from GenBank, IncHI1B plasmids carrying virulence genes and IncFII ones with blaKPC were responsible for both 23 strains respectively.ConclusionsPositive rates of virulence genes vary remarkably in K. pneumoniae. Genes iucA, p-rmpA2 and p-rmpA were primary ones inducing Hv-blaKPC(+)-KP. IncHI1B plasmids carrying virulence genes and IncFII ones with blaKPC constitute the primary combination responsible for Hv-blaKPC(+)-KP. The making of Hv-blaKPC(+)-KP is mostly via blaKPC(+)-KP acquiring another plasmid harboring virulence genes.

Aerobactin Seems To Be a Promising Marker Compared With Unstable RmpA2 for the Identification of Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae: In Silico and In Vitro Evidence

“…Globally, there is a surge in the international high-risk clones acquiring virulence factors among Kp. Several studies on the acquisition of a virulence plasmid by ST11 KPC-producing Kp are increasingly reported from China, where it is endemic ( Hu et al, 2021 ). Hu and colleagues report the uptake of a virulence plasmid among bla KPC-2 carrying ST11 Kp from various regions in China.…”

“…The IncHI1B virulence plasmid in these isolates carried rmpA and rmpA2 , or rmpA2 alone. Interestingly, two clades of ST11 have been identified in China, which carries different capsule types: clade1 with K64 capsule type and clade2 with K47 capsule type ( Hu et al, 2021 ). Clade1 was associated with increased virulence factors when compared with clade2.…”

“…Amidst the various genomic modifications that the hvKp has undergone over the last decade, the markers for genomic identification have remained a constant despite a lack of clear definition. A combination of genes rmpA , rmpA2 , iucA , iroB , and iroN ( Russo and MacDonald, 2020 ; Hu et al, 2021 ; Russo et al, 2021 ) has been used in identifying hvKp along with determining the pathogenicity in virulence models using mice or Galleria mellonella .…”

Innate Host Defense against <b><i>Klebsiella pneumoniae</i></b> and the Outlook for Development of Immunotherapies

“…Russo et al [9] identified iucA, iroB, rmpA, rmpA2, and peg-334 as gene biomarkers that differentiate hvHp from cKp clinical isolates. In general, the presence of rmpA, rmpA2, and genes-encoding 2 siderophoresaerobactin (iuc) and salmochelin (iro) -are predictors for the hvKp pathotype [116][117][118]. Siderophores are secreted small molecules used by microorganisms to scavenge iron from the host environment [119,120].…”

Antimicrobial Susceptibility, Virulence, and Genomic Features of a Hypervirulent Serotype K2, ST65 Klebsiella pneumoniae Causing Meningitis in Italy

“…The hvKp strains often present colonies on agar plates with the peculiar aspect of hypermucoviscosity, detectable semi-quantitatively by a positive ‘string test’; a widely used method for hvKp identification [ 5 ]. Usually, hvKp variants are susceptible to most antibiotics, except inherently resistant ampicillin, while several virulence factors have been identified [ 6 ]. The majority of hvKp show K1 or K2 capsular serotypes, even though non-K1/K2 serotype hvKp strains have also been reported and some K1/K2 strains are non-hvKp.…”